A family of C. elegans VASA homologs control Argonaute pathway specificity and promote transgenerational silencing

Germline Argonautes direct transcriptome surveillance within peri-nuclear membraneless organelles called nuage. In C. elegans, a family of Vasa-related Germ Line Helicase (GLH) proteins localize in, and promote the formation of nuage called P granules. Previous studies have implicated GLH proteins in inherited silencing but direct roles in amplification of small RNAs, or in target mRNA or Argonatue binding have not been identified. Here we show that GLH proteins compete with each other to control Argonaute pathway specificity, bind directly to Argonaute-target mRNAs and act to promote the amplification of small RNAs required for transgenerational inheritance. We show that the ATPase cycle of GLH-1 regulates its direct binding to the Argonaute WAGO-1 which engages amplified small RNAs. Our findings support a dynamic and direct role for GLH proteins in inherited silencing beyond their role as structural components of nuage.种系Argonaute蛋白（Germline Argonaute）可在被称为生殖质颗粒（nuage）的核周无膜细胞器中介导转录组监测。在秀丽隐杆线虫（C. elegans）中，一类Vasa相关种系解旋酶（GLH）蛋白定位于被称为P颗粒（P granules）的生殖质颗粒中，并促进其形成。既往研究已将GLH蛋白与遗传沉默相关联，但尚未明确其在小RNA（small RNAs）扩增、靶mRNA结合或Argonaute结合中的直接作用。本研究证实，GLH蛋白通过相互竞争以调控Argonaute通路的特异性，可直接结合Argonaute靶向的mRNA，并促进跨代遗传（transgenerational inheritance）所需的小RNA扩增。我们发现，GLH-1的ATP酶循环（ATPase cycle）可调控其与结合扩增型小RNA的Argonaute蛋白WAGO-1的直接结合。本研究结果表明，GLH蛋白作为生殖质颗粒的结构组分之外，在遗传沉默中还发挥动态且直接的调控作用。